MicroRNA-204-5p regulates 3T3-L1 preadipocyte proliferation, apoptosis and differentiation

作者：Du, Jingjing; Zhang, Peiwen; Gan, Mailin; Zhao, Xue; Xu, Yan; Li, Qiang; Jiang, Yanzhi; Tang, Guoqing; Li, Mingzhou; Wang, Jinyong; Li, Xuewei; Zhang, Shunhua^*; Zhu, Li^*

来源：Gene, 2018, 668: 1-7.

DOI：10.1016/j.gene.2018.05.036

• miR-204-5p
• Proliferation
• Apoptosis
• Differentiation

Obesity due to excessive lipid accumulation is closely associated with metabolic diseases such as type 2 diabetes, insulin resistance and inflammation. Therefore, a detailed understanding of the molecular mechanisms that underlie adipogenesis is crucial to develop treatments for diseases related to obesity. Here, we found that the microRNA-204-5p (miR-204-5p) was expressed at low levels in fat tissues from obese mice fed long-term with a high-fat diet (HFD). Overexpression or inhibition of miR-204-5p in vitro in 3T3-L1 preadipocytes significantly inhibited or promoted 3T3-L1 proliferation, respectively, an effect mediated by regulating cell proliferation factors. miR-204-5p also induced preadipocyte apoptosis by directly targeting the 3' UTR region of Bc1-2, reducing the constitutive suppression of Bc1-2 on p53-dependent apoptosis. Interestingly, overexpression of miR-204-5p during adipocyte differentiation significantly increased the number of oil red 0 + cells, triglyceride accumulation and the expression of markers associated with adipocyte differentiation. In contrast, inhibition of miR-204-5p had the opposite effect on 3T3-L1 adipocyte differentiation. Luciferase activity assays and qRT-PCR showed that miR-204-5p regulates adipocyte differentiation by negatively regulating KLF3, a negative regulator of lipogenesis. Taken together, our findings showed that miR-204-5p inhibits proliferation and induces apoptosis of preadipocytes by regulating Bc1-2, but also promotes adipocyte differentiation by targeting KLF3.

• 出版日期2018-8-20
• 单位四川农业大学; 重庆市畜牧科学院